The purpose of these investigations is to identify the structural and functional defects of two genetic fibrinogen variants (fibrinogens Philadelphia I and II), and to characterize the abnormal fibrinogen present in patients with liver disease. For the study of fibrinogens Philadelphia I an II, isolated carboxymethylated A alpha, B beta and gamma chains, N-terminal disulfide knots, and fragments D and E will be prepared and their properties analyzed by SDS-polyacrylamide gel electrophoresis, peptide mapping, and binding affinity of fragments to the normal or abnormal thrombin-treated protein conjugated to Sepharose. Finally, the metabolic properties of normal and abnormal fibrinogen fragments D and E will be studied in rabbits. The abnormal fibrinogen of patients with liver disease will be analyzed by immunoelectrophoresis, SDS-polyacrylamide gel electrophoresis, and DEAE-cellulose chromatography. Functional studies will include measurement of fibrinopeptide release, fibrin monomer aggregation, and the ability to form cross-linked fibrin. The metabolic properties of these fibrinogens will be studied in rabbits. The role of carbohydrate content in the functional properties will be studied. Sialic acid content will be measured by the thiobarbituric acid method after acid hydrolysis, and carbohydrate composition will be determined by gas-liquid chromatography. The functional characteristics of the asialo-derivatives of these fibrinogens, obtained by treatment with Vibrio cholerae neuraminidase, will be studied.